This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Medicinal Chemistry. The Carlier group's interests in Medicinal Chemistry encompass three areas. First, they prepare species-selective inhibitors of acetylcholinesterase (AChE) targeting the malaria mosquito (Anopheles gambiae). Such compounds could be deployed on insecticide treated nets to prevent malaria transmission in sub-Saharan Africa. Second, they use click-chemistry based discovery methods to identify BACE1 (beta-secretase) inhibitors;such compounds could be to useful to prevent Alzheimer's disease. Finally, they prepare novel triple reuptake inhibitors to treat SSRI-resistant depression. Enantioselective Synthetic Methods. Organolithium reagents are ubiquitous in organic synthesis. The Carlier group is interested in developing new stereoselective reactions of organolithium compounds and enolates, and in using computation and multinuclear NMR spectroscopy to determine structures and reaction pathways. Recently they developed an enantioselective alkylation route to a new class of (so-called "quaternary") benzodiazepines. A key feature of this work is the intermediacy of transiently non-racemic ("dynamically chiral") intermediates.